Crizotinib for ROS1-rearranged lung cancer and pulmonary tumor thrombotic microangiopathy under venoarterial extracorporeal membrane oxygenation.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive subtype of pulmonary hypertension (PH) associated with impaired right ventricular adaptation and very poor prognosis in cancer, and its rapid progression makes antemortem diagnosis and treatment extremely difficult. We describe the case of a 35-year-old woman who developed severe PH with subsequent circulatory collapse. The patient was clinically diagnosed with PTTM induced by lung adenocarcinoma harboring the c-ros oncogene 1 (ROS1) rearrangement within 1-2 weeks, while hemodynamics were stabilized by rescue venoarterial extracorporeal membrane oxygenation support. Crizotinib, an oral tyrosine kinase inhibitor targeting anaplastic lymphoma kinase, MET, and ROS1 kinase domains dramatically resolved PH, resulting in more than 3 years of survival. Targeted gene-tailored therapy with mechanical support can improve survival in PTTM.

The causes of acute cough: a tertiary-care hospital study in Japan.

OBJECTIVES: Cough is the most frequent presenting complaint in general practice and has an adverse effect on an individual's well-being. Understanding the causes of cough is critical for appropriate patient management. According to its duration, cough is classified as acute, subacute, and chronic. While acute respiratory infection is considered to be the major cause of acute cough, there is little evidence. METHODS: We retrospectively assessed the prevalence of acute cough in all patients presenting with cough to the respiratory clinic of Japanese Red Cross Wakayama Medical Center from May 2018 to April 2019. We subsequently assessed the causes of acute cough, after stratifying patients with acute cough into two subgroups based on the chest X-ray findings. RESULTS: Among 685 patients (329 males; mean age, 61.8 ± 18.6 years) who presented with cough as a chief complaint, 274 (125 males; mean age, 57.6 ± 20.9 years) reported to have acute cough; chest X-ray abnormalities were detected in 113 of these patients. The most frequent cause of acute cough among 113 patients with chest X-ray abnormalities was pneumonia (55.8%), followed by lung cancer (9.7%) and pneumonia exacerbating asthma (7.1%). Among the 161 patients with acute cough without chest X-ray abnormalities, the most frequent cause was upper respiratory tract infection (57.1%), followed by asthma (23.6%) and cough variant asthma (6.2%). CONCLUSIONS: Cough is the most frequent presenting complaint in general practice. Infections are the most frequent causes of acute cough regardless of the chest X-ray findings.

Correlation of Immune-Related Adverse Events and Effects of Pembrolizumab Monotherapy in Patients with Non-Small Cell Lung Cancer.

PURPOSE: The effects of immune checkpoint inhibitors have been reported to be linked with immune-related adverse events (irAEs). In patients with advanced non-small-cell lung cancer, who tested positive for programmed death-ligand 1 (PD-L1), pembrolizumab, an immune checkpoint inhibitor can be used as a treatment, and it was found to improve overall survival. However, there are only a few reports on the relationship between the therapeutic effects of pembrolizumab in patients with lung cancer and the irAEs of pembrolizumab. The purpose of this study was to determine the correlation between immune-related adverse events and the effects of pembrolizumab monotherapy in patients with non-small-cell lung cancer. PATIENTS AND METHODS: From February 2017 to August 2019, we conducted a retrospective analysis of the effects of pembrolizumab treatment and immune-related adverse events in 94 patients with non-small-cell lung cancer treated with pembrolizumab only. RESULTS: In 63 cases, irAEs were observed. The most common irAE was rash. PD-L1 positivity ≥ 50% tended to cause irAEs. The median progression-free survival (PFS) rates with and without irAEs were 371 days (95% CI, 184-NR) and 67 days (95% CI, 51-87 days), respectively. In a multivariate analysis, irAEs and Eastern Cooperative Oncology Group performance status (PS) were the factors related to PFS. CONCLUSION: In patients with lung cancer, who were treated with pembrolizumab monotherapy, the development of irAEs was likely indicative of the positive effects of pembrolizumab. This novel finding appears to be useful for clinicians who work with pembrolizumab for lung cancer treatment.

Visceral pleural biopsy under medical thoracoscopy for the diagnosis of lung adenocarcinoma.

Medical thoracoscopy is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surface and allows for diagnostic procedures. The diagnostic yield of medical thoracoscopy is high and is generally based on parietal pleural biopsy findings. Pleural biopsies are valuable for a diagnosis. However, visceral pleural biopsies are uncommon because of the risk of prolonged air leak. In this study, we report a rare case of the successful diagnosis of lung adenocarcinoma, based on the findings of visceral pleural biopsy under medical thoracoscopy. To avoid lung injury and pneumothorax, we focused on maintaining the thoracoscope and biopsy forceps in a straight angle as much as possible. While looking straight ahead at the visceral pleural nodule as closely as possible, biopsy samples were carefully obtained while confirming that the normal lung was not held. With careful consideration, visceral pleural biopsies may expand the diagnostic capability of medical thoracoscopy.

Intrapleural urokinase directly under medical thoracoscopy for the diagnosis of tuberculous pleurisy.

Medical thoracoscopy, also called "local anesthetic thoracoscopy" and "pleuroscopy," is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surfaces and channels to conduct diagnostic and therapeutic procedures. However, this technique is not helpful when substantial fibrous adhesions exist. We reported the first case of intrapleural urokinase directly under medical thoracoscopy for the diagnosis of malignant pleural mesothelioma with severe multiloculated pleural effusions in 2019. This is the second report regarding the efficacy of intrapleural urokinase directly under medical thoracoscopy for the diagnosis of multiloculated pleural effusions. Urokinase-induced intrapleural fibrinolysis, which removed the fibrous septa, consequently improved the field of view under endoscopy within only 10 min. Fibrinolytic effect appeared very rapidly. This technique is available for tuberculous pleurisy with severe multiloculated pleural effusion.

Osimertinib Administration as the Primary Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy for Brain Metastasis of De Novo T790M-positive Lung Cancer.

A 69-year-old woman underwent left upper lobectomy for left upper lobe lung adenocarcinoma. She later perceived a left visual field defect, and a brain metastasis was detected on head magnetic resonance imaging (MRI). Epidermal growth factor receptor (EGFR) testing identified two separate EGFR mutations: an L858R mutation in exon 21 and a de novo T790M mutation in exon 20. Treatment with osimertinib was started. After one month, head MRI showed that the brain metastasis had shrunk, and the visual field defect had also improved. In this case, first-line osimertinib was effective for treating brain metastasis of de novo T790M-positive lung cancer.

Endobronchial Manifestation of Methotrexate-induced Lymphoproliferative Disorder.

Lymphoproliferative disorders can occur in patients with autoimmune disorders who undergo long-term methotrexate therapy (MTX-LPD). Although the manifestations of MTX-LPD are diverse, little attention is paid to endobronchial involvement. We herein describe two patients with MTX-LPD who presented with parenchymal pulmonary tumors and endobronchial involvement of LPD; one had lymphomatoid gramulomatosis and the other LPD. The patients had no tumors adjacent to the endobronchial lesions. The endobronchial findings included multiple protruded mucosal lesions covered with white material, which was pathologically consistent with LPD. Recognition of the findings may help in making an earlier diagnosis of MTX-LPD in appropriate settings.

Sarcoid-Like Granulomatosis Induced by Nivolumab Treatment in a Lung Cancer Patient.

Nivolumab, an anti-PD-1 antibody, inhibits binding between PD-1 and PD-1 ligand and activates antigen-specific T cells that have become unresponsive to cancer cells. Although it is recommended as a second-line therapy in gene mutation-negative non-small-cell lung cancer, interstitial pneumonia is a well-known side effect of the drug; however, granulomatous lesions have rarely been reported. We describe the case of an 81-year-old male with cT1aN2M1b stage IV pleomorphic carcinoma of the left upper lobe of the lung. After primary treatment with carboplatin and paclitaxel, recurrence was observed in the left supraclavicular lymph node and left adrenal gland. We initiated the administration of nivolumab as a secondary treatment. Reduction was observed in the swelling of the left supraclavicular lymph node and left adrenal gland, but the tumor shadow in the right upper lobe appeared to increase. Bronchoscopy was performed, and the biopsy result showed granulomas; the findings resembled a sarcoid-like granulomatous reaction. The shadows eventually disappeared with nivolumab discontinuation; thus, we concluded that the sarcoid-like granulomatous reaction had resulted from nivolumab administration. Based on our observations, we suggest that when invasive shadows are observed after nivolumab administration, it is necessary to differentiate between disease progression and interstitial pneumonia. Moreover, the decision to reinitiate nivolumab treatment requires careful judgment in future instances of cancer recurrence.

Pleuritis Caused by Mycobacterium kyorinense without Pulmonary Involvement.

We herein describe the first known case of pleuritis caused by Mycobacterium kyorinense without pulmonary involvement. A 48-year-old man undergoing immunosuppressant therapy presented with cough and dyspnea. An accumulation of pleural fluid was noted; however, computed tomography revealed no pulmonary lesions. Cultures of the fluid yielded non-tuberculous mycobacteria, which was identified as Mycobacterium kyorinense. The patient recovered after 6 months of therapy with clarithromycin and moxifloxacin. Clinicians should be aware that Mycobacterium kyorinense can cause pleuritis without pulmonary involvement. When mycobacterial species are isolated from the pleural fluid, precise identification and drug susceptibility testing are warranted.

Desmoplastic Small Round Cell Tumor of the Pleura Successfully Treated with a Lower Dose of Pazopanib.

Desmoplastic small round cell tumor (DSRCT) is an aggressive mesenchymal tumor which primarily affects the abdomen. Even a multimodal approach rarely achieves durable remission and the optimal therapy for extended disease is unknown. We herein describe a rare case of DSRCT arising from the pleura in a 32-year-old man. Initial therapy, which included chemotherapy, surgery and radiotherapy, achieved a partial response for only two months. Although salvage chemotherapies had no effect, pazopanib treatment shrank the tumors and was well-tolerated on an outpatient basis. From the viewpoint of quality of life, pazopanib may therefore be a good therapeutic option for this aggressive disease.

[Cervical lymphadenitis caused by Mycobacterium avium in an immunocompetent adult].

Cervical lymphadenitis due to Mycobacterium avium complex is relatively common in children but is extremely rare in adults, except in immunocompromised patients. In this report, we describe a case of isolated cervical lymphadenitis in an immunocompetent adult woman. Histological examination of the excised lymph node showed multiple epithelioid cell granulomata with necrosis. Further, from the biopsy specimen cultures, we identified the causative organism as Mycobacterium avium. The patient was not administered any antimycobacterial agents because the affected lymph node was removed completely and because of uncertainty regarding the benefits of such treatment. No recurrence was observed in the patient's neck region during postoperative follow-up at 8 months.

[Development of cervical tuberculous lymphadenitis in a patient with Crohn's disease receiving infliximab despite of chemoprophylaxis with isoniazid].

We herein report a case of a 41-year-old female with a 14-year history of Crohn's disease who had been treated with diet and mesalazine. Because of inadequate control, therapy with infliximab was planned. She had a positive result on the interferon-gamma release assay (QuantiFERON TB). After active tuberculosis was ruled out by chest x-ray and computed tomography, she was started on a six-month course of isoniazid 7 weeks prior to starting infliximab. After 10 doses of infliximab (15 months of therapy), she presented with pain of cervical lymphadenopathy. A biopsy of the lymph nodes revealed Langhans giant cells from granulomas and a positive result of polylmerase chain reaction for Mycobacterium tuberculosis. The treatment with infliximab was discontinued and anti-tuberculosis therapy was started. Although treatment for latent tuberculosis infection lowers the risk of reactivation of tuberculosis due to tumor necrosis factor alpha-blockers, it cannot completely inactivate tuberculosis. Despite the completion of chemoprophylaxis, patients receiving such agents should be instructed to watch out for any symptoms associated with pulmonary and extrapulmonary tuberculosis such as fever, cough, malaise, body weight loss, night sweating and lymphadenopathy, and they should also be closely followed up.

[The prevalence of cigarette smoking among asthmatic adults and association of smoking with emergency department visits].

UNLABELLED: We examined the prevalence of cigarette smoking among adults with acute asthma and the relationship between smoking status and visits to the emergency department of a hospital. SETTING AND PATIENTS: 198 subjects (79 men), in whom acute asthma had been newly diagnosed by physicians in a municipal hospital in 2005, were included in this study. RESULTS: Thirty-five percent of the enrolled asthmatic patients were current smokers with a mean of 21 pack-years, while 18% were former smokers, and 47% were never-smokers. The current smokers comprised 41% of all male patients and 31% of all female patients in this study. In the asthmatic patients aged 50 or older, 27% of men and 13% of women were current smokers, while in those younger than 50, the same percentages were 59% and 50%, respectively. Since July 31, 2007, 6 current smokers (8.7%) had visited the emergency department due to asthmatic attacks, while 3 (8.3%) were ex-smokers and 1 (1.1%) was a never-smokers (p < 0.011). CONCLUSION: Cigarette smoking was common among patients with acute asthma, especially younger women. A current-smoker status is therefore considered to be associated with emergency visits to hospitals due to asthmatic attacks.

[A case of cryptococcal pneumonia accompanying meningitis].

UNLABELLED: Cryptococcosis is a fungal infection caused by cryptococcus neoformans. Cryptococcal pneumonia occurs due to inhalation of the organism into the respiratory tract, sometimes accompanied by meningitis in immunocompromised patients, and can be life-threatening. We report a case of cryptococcal meningitis occurring during corticosteroid therapy for rheumatoid arthritis. CASE: A 82-year-old woman with rheumatoid arthritis was given a diagnosis of cryptococcal meningitis, and improved after administeration of amphotericin B in combination with flucytosine. However 3 weeks later, side effects occurred, she was given fluconazole alone, but her condition worsened and she died. In severe cases of cryptococcal meningitis, we should take into account drug susceptibility tests and drug concentrations at the site of infection.

[Two cases of herpes simplex esophagitis during treatment for lung cancer].

Herpes simplex virus (HSV) is one of the three major causes of infectious esophagitis, along with Candida albicans and Cytomegalo virus (CMV). Most cases occur in immunocompromised hosts, in whom this can be life threatening. We report two cases of herpes simplex esophagitis occurring during treatment for lung cancer. Case 1: An 80-year-old man with radiation pneumonia caused by radiotherapy for lung cancer was admitted for treatment with antibiotics and corticosteroids. Shortly after initiation of treatment, he complained of dysphasia. Endoscopic examination revealed herpes simplex esophagitis. Case 2: A 71-year-old man was given corticosteroids for cryptogenic organizing pneumonia following chemotherapy for lung cancer. During treatment, the patient complained of odynophagia. Endoscopic examination revealed herpes simplex esophagitis. Both cases died due to progression of lung cancer and acute respiratory distress syndrome, despite administration of acyclovir. When immunocompromised patients complain of prolonged dysphagia and odynophagia, the presence of herpes simplex esophagitis should be clarified by endoscopic examination. It is occasionally difficult to distinguish between HSV and Candida esophagitis by endoscopic observation alone. Esophageal mucosal endoscopic cytology can help differentiate between these three infectious agents.

[A case of severe adult-onset Still' s disease presenting with pleuropericarditis].

Adult-onset Still' s disease (AOSD) is an uncommon rheumatic disease characterized by high spiking fever, arthritis, an evanescent skin rash and variety of systemic symptoms, though initial onset of pleuropulmonary manifestation is relatively rare and could be responsible for a delay in diagnosis. We report a case of AOSD presenting with pleuritis with concomitant pericardial effusion. A 42-year-old Japanese man was admitted with a spiking fever of 40 degrees C, hyperleucocytosis (21.6 x 10(9)/l), and a high titer of C-reactive protein (16.84mg/dl). Chest X-ray film and computed tomography showed bilateral pleural effusion and massive pericardial effusion which both required tube drainage. Analyses of fluids revealed that both were exudative and sterile, and pleural biopsy showed nonspecific inflammation with mild fibrosis. Neither antibiotics nor antituberculosis drugs were effective. Rash, hepatosplenomegaly, polyarthritis, pharyngitis and right hypochondralgia were accompanied by serum hyperferritinemia. After exclusion of the possibility of infection, other connective tissue disease and malignancy, a diagnosis of AOSD was made. Improvement was not observed with nonsteroidal anti-inflammatory drug and corticosteroid therapy. Double filtration plasmapheresis (DFPP) following steroid pulse therapy alleviated the symptoms and the laboratory data immediately and corticosteroids could be tapered. DFPP is a safe therapeutic procedure and can be an alternative for refractory AOSD.

[Pulmonary infection caused by Mycobacterium szulgai: a case report].

We reported a case of pulmonary infection caused by Mycobacterium szulgai (M. szulgai) in an immunocompetent, asymptomatic 55-year-old man without underlying disease. A chest radiograph of an annual health examination revealed a right upper lobe infiltrate with thin-walled cavities, which was not present in the previous year. An acid-fast stain of bronchial washing fluid was positive, and antimycobacterial chemotherapy with isoniazid (400 mg/day), rifampin (450 mg/day), and ethambutol (750 mg/day) was initiated on presumptive diagnosis of the case as tuberculosis. DNA-DNA hybridization of sputum and bronchial washing samples identified M. szulgai as the causative organism. Antimicrobial susceptibility testing indicated that the isolate was sensitive to most common antimycobacterial drugs except capreomycin (CPM) and p-aminosalicylic acid (PAS), and was also sensitive to clarithromycin and fluoroquinolones including ofloxacin, levofloxacin, sparfloxacin, and ciprofloxacin. After 12 months of therapy, a repeat chest radiograph demonstrated improvement of the right upper lobe infiltrate. When M. szulgai is isolated, it almost always represents a true pathogen. Therefore, the detection of even a small number of M. szulgai warrants treatment based on susceptibility testing.